Medical Chemistry Center of Togliatti State University has obtained its own human stem cell lines, which makes it possible to grow unlimited numbers of cell samples of various organs, including the heart, necessary for the research.
The appearance of new tools allows Togliatti scientists to conduct anticancer drug trials on heart, brain, liver, and kidneys cells that were obtained in the laboratory. Attention will be mainly paid to the research on heart cells, since the negative impact on heart tissue, or cardiotoxicity is one of the most common side effects of these drugs.
Work on obtaining cell lines of human induced pluripotent stem cells (hiPSC) has been carried out at Togliatti State University since the end of 2019 as a part of the OpenHTS project by TSU Medical Chemistry Center.
The project aims to find new anticancer agents. Anticancer drug trials are conducted on both tumor and healthy cells: it is important for scientists not only to understand whether the substance kills cancer cells, but also to evaluate the effect of a potential drug on healthy cells.
Healthy cells can be obtained directly from donors, but it requires a complex procedure of biopsy – the sampling of biological material from a particular organ. The second option for obtaining healthy cells for research is to grow them in the laboratory – that is what the researchers of TSU Medical Chemistry Center have done.
The development of Togliatti scientists is based on the breakthrough of Japanese doctor Shinya Yamanaka, who was awarded the Nobel Prize for Physiology or Medicine. He showed that mature organ and tissue cells can be returned to their embryonic state by converting them into “universal”, or so-called induced pluripotent cells (they are also known as stem cells). Such “embryonic” cells can be transformed into “building material” necessary for the tissue regeneration of heart, brain, liver and other human organs.
This principle of “reprogramming” cells into stem cells allows scientists to grow cells of necessary organs in the laboratory, such as the heart (cardiomyocytes) or liver (hepatocytes), and also to conduct high-quality screening studies on them.
Buying already formed stem cell lines is an expensive business, growing them is also not cheap: one line will cost about 800 thousand rubles. But since this is a very promising topic for world science, and no one is doing this in the Samara region, TSU scientists took this case – and were able to get their own cell lines, later turning them into heart cells.
As a result, there was a “tissue-like” structure that can contract: the “heart” begins to beat (you can see it in the microscope and in the attached video), and TSU scientists were able to conduct toxicity studies on it. The substances required for studies are sent to TSU Medical Chemistry Center from organizations and universities that are partners in the OpenHTS project (including Peoples’ Friendship University of Russia, Belarusian State University, Saint Petersburg State University, and others) – about 15 of them in total.
The decision of Togliatti scientists to get heart cells in the first place wasn’t an accident: the TSU Medical Chemistry Center is actively engaged in searching for modern anticancer agents. It is cardiotoxicity (a pathological effect on the heart tissue) which is the frequent negative effect of these drugs.
“The process of developing any new drug is very long and expensive, a side effect can often appear at any stage of testing and cancel out all the work done by scientists,” said Alexander Bunev, the director of TSU Medical Chemistry Center.
“People have their own genetic characteristics, burdened with chronic diseases, and no company at the early stages of drug development can start human clinical testing on all people immediately. Therefore, scientists are looking for the new tools to test drugs as effectively as possible, cutting off side effects as early as possible,” said Alexander.
“The discovery of a Japanese colleague made it possible to obtain induced pluripotent cells that can be easily grown in the laboratory and, under certain “rules of the game”, turned into heart cells, completely preserving the genetic traits of the donor. What’s better: to do ten heart biopsies to collect biomaterial, or to conduct such a study in the laboratory? Thanks to the donation of a piece of skin or 5 milliliters of blood, we have the opportunity to have “millions of people” in one test tube,” Alexander continued.
“In fact, we get a new cell panel made up of different “donors” – as if the drug has been tested on many people.”
Anticancer drugs produced in the laboratory of TSU belong to the target type: they do not poison the entire human body, but target a specific protein in the cancer cell. Simultaneously, scientists plan to test their development on healthy cells, getting the opportunity to predict the most common side effects.
Despite the fact that a number of approaches are used to evaluate and avoid side effects at an early stage of drug development (for example, computer simulation), experimental evaluation always has the last word. And thanks to their own tools, TSU scientists can conduct it repeatedly, to the extent appropriate, meeting all the requirements for developing innovative tools to fight cancer.
In addition, the collection of cell lines from the largest possible number of donors will allow to conduct more advanced phenotypic (taking into account individual characteristics) screening, which will not only strengthen the scientific perspective of Togliatti State University but also increase its attractiveness in the market of research offered to the large pharmaceutical companies.